Maintenance of stable body weight is achieved via a biological process known as energy homeostasis, which matches cumulative energy intake to expenditure over time. Obesity is the most common disorder of energy homeostasis and, because of its increasing prevalence and strong links to metabolic and cardiovascular diseases, is a leading cause of mortality worldwide. Energy homeostasis involves humoral signals such as leptin that create a circuit between peripheral tissues involved in energy storage and utilization and central networks controlling energy balance. Understanding of how defects in this homeostatic system cause obesity is critical for the development of new, more effective forms of obesity therapy. This symposium will focus on molecular, genetic, cellular and physiological aspects of normal and abnormal energy homeostasis and on the application of new technologies to their study. Progress towards improved therapeutic options for obesity and their implications for public health and public policy will be emphasized.